Radiopaque polymers

Abstract

This invention relates to radiopaque polymers and to their use, particularly in the manufacture of medical devices and in methods of medical treatment, including therapeutic embolization. In particular embodiments the present disclosure relates to a hydrophilic polymer comprising pendent groups which a phenyl ring is substituted with one or more iodine groups and one or more non-iodine groups as described in more detail herein.

The invention claimed is: 
     
       1. A hydrophilic polymer comprising pendent groups of the formula I: 
       
         
           
           
               
               
           
         
         wherein: 
         W is independently selected from —OH, —COOH, —SO 3 H, —OPO 3 H, —O—(C 1-4  alkyl), —O—(C 1-4  alkyl)OH, —O—(C 1-4  alkyl)R 2 , —O—(C 2 H 5 O) q R 1 , —(C═O)—O—C 1-4  alkyl and —O—(C═O)C 1-4  alkyl, where —OH, —COOH, —O—PO 3 H and —SO 3 H may be in the form of a pharmaceutically acceptable salt; or a group —BZ; 
         B is a bond, or a straight branched alkanediyl, oxyalkylene, alkylene oxaalkylene, or alkylene group, optionally containing one or more fluorine substituents; and 
         Z is an ammonium, phosphonium, or sulphonium phosphate or phosphonate ester zwitterionic group; 
         X is either a bond or a linking group having 1 to 8 carbons and optionally 1 to 4 heteroatoms selected from O, N and S; 
         G is a coupling group through which the group of the formula I is coupled to the polymer and is selected from 1,3-dioxolane and 1,3 dioxane; 
         R 1  is H or C 1-4  alkyl; 
         R 2  is —COOH, —SO 3 H, or —OPO 3 H 2    
         q is an integer from 1 to 4; 
         n is an integer from 1 to 4; 
         p is an integer from 1 to 3; and 
         n+p is from 2 to 5. 
       
     
     
       2. The polymer of  claim 1  which is a polyhydroxylated polymer. 
     
     
       3. The polymer of  claim 1  which is a co-polymer of polyvinyl alcohol and wherein the groups of the formula I are coupled through hydroxyl groups of the polyvinyl alcohol. 
     
     
       4. The polymer of  claim 1  in which n is two or three. 
     
     
       5. The polymer of  claim 1  in which the phenyl ring of the group of the formula I is 3,5 diiodinated, 3,4,5 triiodinated or 2,4,6 triiodinated. 
     
     
       6. A polymer according to  claim 1  in which p is 1. 
     
     
       7. The polymer of  claim 1  in which W is independently selected from —OH, —COOH, —SO 3 H, —OPO 3 H 2 , —O—(C 1-4  alkyl), —O—(C 1-4  alkyl)OH, —O—(C 1-4  alkyl)R 2 , —O—(C 2 H 5 O) q R 1 , —(C═O)—O—C 1-4  alkyl and —O—(C═O)C 1-4  alkyl, where —OH, —COOH, —O—PO 3 H and —SO 3 H may be in the form of a pharmaceutically acceptable salt, or a group —BZ, wherein B is a bond, a branched or non-branched C 1-6  alkanediyl group or a branched or non-branched C 1-6  oxyalkylene group; and
 Z is a group of formula II 
 
       
         
           
           
               
               
           
         
         wherein A 3  and A 4 , are the same or different and are selected from —O—, —S—, and —NH—; and 
         —W 1+  is —W 2 —N + R 4   3 , in which W 2  is C 1-6  alkanediyl and R 4  are the same or different and each is hydrogen or C 1-4  alkyl. 
       
     
     
       8. The polymer of  claim 1  in which W is selected from —OH, —COOH, —SO 3 H, —OPO 3 H 2 , —O—(C 1-4  alkyl)R 2  and —O—(C 2 H 5 O) q R 1 ; wherein —OH, —COOH, —OPO 3 H 2  and —SO 3 H may be in the form of a pharmaceutically acceptable salt. 
     
     
       9. The polymer  claim 1  in which the phenyl ring of the group of the formula I is substituted in one of the following patterns: 
       
         
           
           
               
               
           
         
       
     
     
       10. The polymer of  claim 1  which is cross-linked. 
     
     
       11. The polymer of  claim 1  in the form of a hydrogel comprising greater than 50% water wt/wt. 
     
     
       12. The polymer of  claim 1  having an iodine content of greater than 10 mg iodine per cm 3  of fully hydrated polymer. 
     
     
       13. The polymer of  claim 1  which has a radiodensity of greater than 500 HU. 
     
     
       14. The polymer of  claim 1  which has a radiodensity of greater than 1000 HU. 
     
     
       15. The polymer of  claim 1  which is substituted by groups, other than those in W, which are charged at pH 7.4. 
     
     
       16. A flowable composition comprising the polymer of  claim 1 . 
     
     
       17. A composition comprising the polymer of  claim 1 . 
     
     
       18. The composition comprising the polymer of  claim 17 , as a solution in either an aqueous solvent or organic solvent which is miscible with water. 
     
     
       19. The polymer of  claim 1  in which p is 2 or 3.